The plasma membranes of transformed cells show increased rates of nutrient transport, decreased responsiveness of the adenylate cyclase enzyme to hormonal stimulation and abnormalities in protein composition. These abnormalities are thought to account at least in part for the loss of growth control and tumorigenicity observed in transformed cells. It has, however, not been possible to show how plasma membrane functions are regulated in either normal or transformed cells nor how changes in membrane function effect cell growth and differentiation. Since in many systems modulation in proteinphosphorylation-dephosphorylation has been shown to regulate biological events, we initiated a series of studies to determine if differences could be detected in the ability of plasma membrane proteins of normal and transformed cells to undergo cyclic AMP-dependent phosphorylation. We have recently reported that the membranes of density-inhibited 3T3 cells show prominent cyclic AMP-dependent membrane phosphorylation, but that the plasma membranes of methylcholathrene transformed cells show no cyclic AMP-dependent phosphorylation and the membranes of virally transformed cells showed significantly reduced phosphorylation during the cell cycle and with cell differentiation and that transformed cells do not. Current studies are directed at determining the basic defect in transformed cells that prevent normal plasma membrane phosphorylation and at determining the function of membrane phosphoproteins and their role in control of cell growth and differentiation.